Pain affects one quarter of the US population, and is a common cause to seek medical care. C-fibers transduce noxious stimuli into electric signals and release neurotransmitters, such as calcitonin gene-related peptide (CGRP), to signal painful stimuli to the spinal cord and central nervous system. Inflammation causes C-fibers to release more CGRP, which induces symptoms of chronic pain states, including hyperalgesia and allodynia. Exposure to nerve growth factor (NGF), an inflammatory mediator, increases CGRP content in sensory neurons and increases the release of CGRP independent of changes in content, i.e. NGF sensitizes sensory neurons such that vesicular release increases per stimulus. Sensitization and increased CGRP content in neurons cause hyperalgesia and allodynia. Exploring the regulation of CGRP content and release in sensory neurons is critical to the development of treatments for these symptoms. We propose to study the intracellular signaling molecules that mediate the effects of NGF. The Ras pathway is implicated in the regulation of CGRP release in neurons. Downstream effectors of Ras, such as the mitogen-activated protein kinase (MAPK), cause sensitization of sensory neurons in response to a stimulus. Furthermore, NGF activates the Ras pathway in other cell systems. We propose to establish whether there is a direct relationship between the activation of the Ras pathway and NGF-induced increases in total cell CGRP content and vesicular release from sensory neurons.